Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, Chronic Obstructive Pulmonary Disease, Chronic Bronchitis, Emphysema, Airflow Obstruction, Chronic, Chronic Airflow Obstruction, Chronic Obstructive Airway Disease, Chronic Obstructive Lung Disease
Brief summary
The purpose of this Phase III study is to evaluate the long-term safety and tolerability of two fixed-dose combinations of inhaled aclidinium bromide/formoterol fumarate, aclidinium bromide, formoterol fumarate and placebo in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD). Long-term efficacy, pharmacoeconomic and health-related quality of life assessments will also be evaluated. This extension study will include a 28 week treatment period, followed by a four week follow up visit. All patients will remain in the same treatment group as for the lead-in study and continue on one of the four treatment arms or placebo.
Interventions
DRUGAclidinium bromide/formoterol Fixed-Dose Combination (FDC)
Inhaled Aclidinium bromide/formoterol Fixed-Dose Combination (FDC) high dose, twice per day
Inhaled Aclidinium bromide 400 μg, twice per day
DRUGFormoterol Fumarate
Inhaled Formoterol Fumarate 12 μg, twice per day
DRUGPlacebo
Inhaled dose-matched placebo, twice per day
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Completion of the treatment phase of the lead-in study, LAC-MD-31 * Written informed consent obtained from the patient before the initiation of any study specific procedures * No medical contraindication as judged by the PI * Compliance with LAC-MD-31 study procedures and IP dosing.
Exclusion criteria
* No specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients to Experience Any Treatment-emergent Adverse Event | Baseline of lead-in study to follow-up call 14±3 days after last dose of investigational product (up to Week 52) | For each safety parameter, the last assessment made before the first dose of investigational product in the lead-in study (LAC MD-31) was used as the baseline for all analyses of that safety parameter in this extension study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Clinical Laboratory Values for Hematology, Chemistry or Urinalysis | Baseline of lead-in study to end of treatment (up to Week 52) | Potentially clinically significant change: \>1.15 × upper limit of normal (ULN) for absolute cell count of basophils, eosinophils or monocytes, blood alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, total cholesterol, creatine kinase, creatinine, gamma glutamyl transferase, lactate dehydrogenase, triglycerides or uric acid \<0.85 x lower limit of normal (LLN) or \> 1.15 ULN for hematocrit ratio, haemoglobin, lymphocytes or neutrophils absolute cell count, platelet count (thrombocytes), red or white blood cell count, calcium, fasting glucose, phosphorus, total protein, or urinary pH \<0.95 x LLN or \>1.05 x ULN for chloride, potassium, sodium Urinary glucose ≥0.015, blood or ketones or protein ≥1 or specific gravity \>1.1 × ULN The last assessment made before the first dose of investigational product in the lead-in study was used as the baseline for all safety analyses in the extension study |
| Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | Baseline of lead-in study to end of treatment (up to Week 52) | — |
| Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Vital Signs (Pulse Rate, Systolic or Diastolic Blood Pressure or Weight) | Baseline of lead-in study to end of treatment (up to Week 52) | Potentially clinically significant change: Systolic BP ≥180 mmHg and increase ≥20 mmHg from baseline or ≤90 mmHg and decrease ≥20 mmHg from baseline Diastolic BP ≥105 mmHg and increase ≥15 mmHg from baseline or ≤50 mmHg and decrease ≥15 mmHg from baseline Pulse rate ≥110 bpm and increase ≥15% from baseline or ≤50 bpm and decrease ≥15% from baseline Weight increase or decrease ≥7% from baseline The last assessment made before the first dose of investigational product in the lead-in study was used as the baseline for all safety analyses in the extension study |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 1-hour Morning Post-dose Forced Expiratory Volume in One Second (FEV1) | Baseline of lead-in study to Week 52 of treatment | — |
| Change From Baseline in Morning Predose (Trough) Forced Expiratory Volume in One Second (FEV1) | Baseline of lead-in study to Week 52 of treatment | — |
| Transition Dyspnea Index (TDI) Focal Score at End of Study | Baseline of lead-in study to Week 52 of treatment | The TDI measures the change from baseline in severity of breathlessness in symptomatic patients. The TDI contains a rating for 3 categories (functional impairment, magnitude of task, magnitude of effort). TDI scale ranges from -3 (major deterioration) to +3 (major improvement) including a 0 score to indicate no change. The 3 categories are added to obtain a focal score ranging from -9 (including 0) to +9. |
| Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score | Baseline of lead-in study to Week 52 of treatment | St George's Respiratory Questionnaire (SGRQ) measures COPD-specific health outcomes and consists of 3 dimension scores (symptom, activity and impact). SGRQ total score is the sum of these scores and ranges from 0 (best health status) to 100 (worst health status). |
Countries
Australia, Canada, New Zealand, United States
Participant flow
Recruitment details
This study was conducted at 169 study centers, 160 in the United States, and 9 in Canada. The first patient was screened in April 2012 and the last patient visit was in June 2013
Pre-assignment details
This was a double-blind, placebo- and active-controlled, 28-week treatment, extension study of the lead-in study, Study LAC-MD-31 Those patients who chose to continue the treatment in the extension study and met the eligibility for the extension study remained on the same treatment as they were randomized to in the lead-in study
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo administered BID by inhalation | 146 |
| Aclidinium/Formoterol 400/12 μg Aclidinium bromide 400 μg + formoterol fumurate 12 μg fixed dose combination (FDC) administered BID by inhalation | 182 |
| Aclidinium/Formoterol 400/6 μg Aclidinium bromide 400 μg + formoterol fumurate 6 μg fixed dose combination (FDC) administered BID by inhalation | 204 |
| Aclidinium 400 μg Aclidinium bromide 400 μg administered BID by inhalation | 194 |
| Formoterol 12 μg Formoterol fumurate 12 μg administered BID by inhalation | 192 |
| Total | 918 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Extension Study | Adverse Event | 7 | 6 | 5 | 6 | 4 |
| Extension Study | Lack of Efficacy | 2 | 3 | 3 | 2 | 2 |
| Extension Study | Lost to Follow-up | 6 | 2 | 0 | 3 | 3 |
| Extension Study | Protocol Violation | 0 | 4 | 3 | 4 | 3 |
| Extension Study | Site termination/COPD exacerbation/other | 3 | 8 | 4 | 6 | 6 |
| Extension Study | Withdrawal by Subject | 7 | 6 | 11 | 8 | 14 |
| Lead-in Study | Adverse Event | 21 | 21 | 22 | 16 | 14 |
| Lead-in Study | Lack of Efficacy | 20 | 5 | 4 | 8 | 10 |
| Lead-in Study | Lost to Follow-up | 5 | 9 | 4 | 2 | 4 |
| Lead-in Study | Protocol Violation | 19 | 10 | 12 | 13 | 21 |
| Lead-in Study | Site termination/COPD exacerbation/other | 14 | 10 | 8 | 9 | 9 |
| Lead-in Study | Withdrawal by Subject | 22 | 11 | 12 | 24 | 11 |
Baseline characteristics
| Characteristic | Placebo | Aclidinium/Formoterol 400/12 μg | Aclidinium/Formoterol 400/6 μg | Aclidinium 400 μg | Formoterol 12 μg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 63.2 Years STANDARD_DEVIATION 8.6 | 63.7 Years STANDARD_DEVIATION 9.1 | 63.6 Years STANDARD_DEVIATION 9.2 | 62.9 Years STANDARD_DEVIATION 8.3 | 62.8 Years STANDARD_DEVIATION 8.7 | 63.2 Years STANDARD_DEVIATION 8.8 |
| Sex: Female, Male Female | 65 Participants | 94 Participants | 84 Participants | 90 Participants | 102 Participants | 435 Participants |
| Sex: Female, Male Male | 81 Participants | 88 Participants | 120 Participants | 104 Participants | 90 Participants | 483 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 37 / 146 | 59 / 182 | 64 / 204 | 67 / 194 | 62 / 192 |
| serious Total, serious adverse events | 10 / 146 | 14 / 182 | 14 / 204 | 15 / 194 | 14 / 192 |
Outcome results
Primary
Percentage of Patients to Experience Any Treatment-emergent Adverse Event
For each safety parameter, the last assessment made before the first dose of investigational product in the lead-in study (LAC MD-31) was used as the baseline for all analyses of that safety parameter in this extension study
Time frame: Baseline of lead-in study to follow-up call 14±3 days after last dose of investigational product (up to Week 52)
Population: The Extension Safety Population defined as all patients from the lead-in study (LAC-MD-31) who signed informed consent at Visit 1 of this extension study (last visit of the lead-in study) and who took at least 1 dose of double-blind investigational product in this extension study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients to Experience Any Treatment-emergent Adverse Event | 56.8 Percentage of participants |
| Aclidinium/Formmoterol 400/12 μg | Percentage of Patients to Experience Any Treatment-emergent Adverse Event | 65.9 Percentage of participants |
| Aclidinium/Formoterol 400/6 μg | Percentage of Patients to Experience Any Treatment-emergent Adverse Event | 61.3 Percentage of participants |
| Aclidinium 400 μg | Percentage of Patients to Experience Any Treatment-emergent Adverse Event | 67.5 Percentage of participants |
| Formoterol 12 μg | Percentage of Patients to Experience Any Treatment-emergent Adverse Event | 64.6 Percentage of participants |
Secondary
Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value
Time frame: Baseline of lead-in study to end of treatment (up to Week 52)
Population: The Extension Safety Population defined as all patients from the lead-in study (LAC-MD-31) who signed informed consent at Visit 1 of this extension study (last visit of the lead-in study) and who took at least 1 dose of double-blind investigational product in this extension study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcB change from baseline >30 msec | 36.3 Percentage of participants |
| Placebo | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | Heart rate ≤50 bpm & ≥15% decrease from baseline | 11.0 Percentage of participants |
| Placebo | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcB >480 msec | 7.5 Percentage of participants |
| Placebo | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | Heart rate ≥110 bpm & ≥15% increase from baseline | 0.7 Percentage of participants |
| Placebo | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | PR interval ≥200 msec & ≥25% increase | 2.8 Percentage of participants |
| Placebo | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QT interval >480 msec | 3.4 Percentage of participants |
| Placebo | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QT interval change from baseline >30 msec | 53.4 Percentage of participants |
| Placebo | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QRS interval ≥100 msec & ≥25% increase | 6.2 Percentage of participants |
| Placebo | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcF >480 msec | 2.1 Percentage of participants |
| Placebo | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcF change from baseline >30 msec | 27.4 Percentage of participants |
| Aclidinium/Formmoterol 400/12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QT interval >480 msec | 3.8 Percentage of participants |
| Aclidinium/Formmoterol 400/12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QT interval change from baseline >30 msec | 53.8 Percentage of participants |
| Aclidinium/Formmoterol 400/12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcB change from baseline >30 msec | 37.0 Percentage of participants |
| Aclidinium/Formmoterol 400/12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcB >480 msec | 8.3 Percentage of participants |
| Aclidinium/Formmoterol 400/12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcF change from baseline >30 msec | 28.7 Percentage of participants |
| Aclidinium/Formmoterol 400/12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcF >480 msec | 0.6 Percentage of participants |
| Aclidinium/Formmoterol 400/12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QRS interval ≥100 msec & ≥25% increase | 6.6 Percentage of participants |
| Aclidinium/Formmoterol 400/12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | PR interval ≥200 msec & ≥25% increase | 2.2 Percentage of participants |
| Aclidinium/Formmoterol 400/12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | Heart rate ≥110 bpm & ≥15% increase from baseline | 2.7 Percentage of participants |
| Aclidinium/Formmoterol 400/12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | Heart rate ≤50 bpm & ≥15% decrease from baseline | 6.0 Percentage of participants |
| Aclidinium/Formoterol 400/6 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcF >480 msec | 1.0 Percentage of participants |
| Aclidinium/Formoterol 400/6 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | Heart rate ≥110 bpm & ≥15% increase from baseline | 1.0 Percentage of participants |
| Aclidinium/Formoterol 400/6 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcB change from baseline >30 msec | 39.7 Percentage of participants |
| Aclidinium/Formoterol 400/6 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcB >480 msec | 9.8 Percentage of participants |
| Aclidinium/Formoterol 400/6 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QT interval >480 msec | 2.9 Percentage of participants |
| Aclidinium/Formoterol 400/6 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcF change from baseline >30 msec | 30.4 Percentage of participants |
| Aclidinium/Formoterol 400/6 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QRS interval ≥100 msec & ≥25% increase | 3.9 Percentage of participants |
| Aclidinium/Formoterol 400/6 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QT interval change from baseline >30 msec | 55.9 Percentage of participants |
| Aclidinium/Formoterol 400/6 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | Heart rate ≤50 bpm & ≥15% decrease from baseline | 8.3 Percentage of participants |
| Aclidinium/Formoterol 400/6 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | PR interval ≥200 msec & ≥25% increase | 1.0 Percentage of participants |
| Aclidinium 400 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QT interval >480 msec | 2.6 Percentage of participants |
| Aclidinium 400 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | Heart rate ≤50 bpm & ≥15% decrease from baseline | 7.2 Percentage of participants |
| Aclidinium 400 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QT interval change from baseline >30 msec | 60.4 Percentage of participants |
| Aclidinium 400 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcB change from baseline >30 msec | 35.6 Percentage of participants |
| Aclidinium 400 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcF >480 msec | 0.5 Percentage of participants |
| Aclidinium 400 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | PR interval ≥200 msec & ≥25% increase | 3.1 Percentage of participants |
| Aclidinium 400 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | Heart rate ≥110 bpm & ≥15% increase from baseline | 1.0 Percentage of participants |
| Aclidinium 400 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QRS interval ≥100 msec & ≥25% increase | 2.6 Percentage of participants |
| Aclidinium 400 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcB >480 msec | 5.7 Percentage of participants |
| Aclidinium 400 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcF change from baseline >30 msec | 27.8 Percentage of participants |
| Formoterol 12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcB >480 msec | 8.4 Percentage of participants |
| Formoterol 12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | Heart rate ≥110 bpm & ≥15% increase from baseline | 2.1 Percentage of participants |
| Formoterol 12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcF change from baseline >30 msec | 30.2 Percentage of participants |
| Formoterol 12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcF >480 msec | 2.6 Percentage of participants |
| Formoterol 12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | Heart rate ≤50 bpm & ≥15% decrease from baseline | 4.7 Percentage of participants |
| Formoterol 12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QRS interval ≥100 msec & ≥25% increase | 4.7 Percentage of participants |
| Formoterol 12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QT interval change from baseline >30 msec | 48.4 Percentage of participants |
| Formoterol 12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | PR interval ≥200 msec & ≥25% increase | 1.6 Percentage of participants |
| Formoterol 12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QTcB change from baseline >30 msec | 38.4 Percentage of participants |
| Formoterol 12 μg | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value | QT interval >480 msec | 4.7 Percentage of participants |
Secondary
Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Clinical Laboratory Values for Hematology, Chemistry or Urinalysis
Potentially clinically significant change: \>1.15 × upper limit of normal (ULN) for absolute cell count of basophils, eosinophils or monocytes, blood alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, total cholesterol, creatine kinase, creatinine, gamma glutamyl transferase, lactate dehydrogenase, triglycerides or uric acid \<0.85 x lower limit of normal (LLN) or \> 1.15 ULN for hematocrit ratio, haemoglobin, lymphocytes or neutrophils absolute cell count, platelet count (thrombocytes), red or white blood cell count, calcium, fasting glucose, phosphorus, total protein, or urinary pH \<0.95 x LLN or \>1.05 x ULN for chloride, potassium, sodium Urinary glucose ≥0.015, blood or ketones or protein ≥1 or specific gravity \>1.1 × ULN The last assessment made before the first dose of investigational product in the lead-in study was used as the baseline for all safety analyses in the extension study
Time frame: Baseline of lead-in study to end of treatment (up to Week 52)
Population: The Extension Safety Population defined as all patients from the lead-in study (LAC-MD-31) who signed informed consent at Visit 1 of this extension study (last visit of the lead-in study) and who took at least 1 dose of double-blind investigational product in this extension study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Clinical Laboratory Values for Hematology, Chemistry or Urinalysis | 32.9 Percentage of participants |
| Aclidinium/Formmoterol 400/12 μg | Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Clinical Laboratory Values for Hematology, Chemistry or Urinalysis | 41.2 Percentage of participants |
| Aclidinium/Formoterol 400/6 μg | Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Clinical Laboratory Values for Hematology, Chemistry or Urinalysis | 35.3 Percentage of participants |
| Aclidinium 400 μg | Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Clinical Laboratory Values for Hematology, Chemistry or Urinalysis | 32.5 Percentage of participants |
| Formoterol 12 μg | Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Clinical Laboratory Values for Hematology, Chemistry or Urinalysis | 38.5 Percentage of participants |
Secondary
Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Vital Signs (Pulse Rate, Systolic or Diastolic Blood Pressure or Weight)
Potentially clinically significant change: Systolic BP ≥180 mmHg and increase ≥20 mmHg from baseline or ≤90 mmHg and decrease ≥20 mmHg from baseline Diastolic BP ≥105 mmHg and increase ≥15 mmHg from baseline or ≤50 mmHg and decrease ≥15 mmHg from baseline Pulse rate ≥110 bpm and increase ≥15% from baseline or ≤50 bpm and decrease ≥15% from baseline Weight increase or decrease ≥7% from baseline The last assessment made before the first dose of investigational product in the lead-in study was used as the baseline for all safety analyses in the extension study
Time frame: Baseline of lead-in study to end of treatment (up to Week 52)
Population: The Extension Safety Population defined as all patients from the lead-in study (LAC-MD-31) who signed informed consent at Visit 1 of this extension study (last visit of the lead-in study) and who took at least 1 dose of double-blind investigational product in this extension study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Vital Signs (Pulse Rate, Systolic or Diastolic Blood Pressure or Weight) | 27.4 Percentage of participants |
| Aclidinium/Formmoterol 400/12 μg | Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Vital Signs (Pulse Rate, Systolic or Diastolic Blood Pressure or Weight) | 24.2 Percentage of participants |
| Aclidinium/Formoterol 400/6 μg | Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Vital Signs (Pulse Rate, Systolic or Diastolic Blood Pressure or Weight) | 18.6 Percentage of participants |
| Aclidinium 400 μg | Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Vital Signs (Pulse Rate, Systolic or Diastolic Blood Pressure or Weight) | 22.2 Percentage of participants |
| Formoterol 12 μg | Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Vital Signs (Pulse Rate, Systolic or Diastolic Blood Pressure or Weight) | 24.5 Percentage of participants |
Other Pre-specified
Change From Baseline in 1-hour Morning Post-dose Forced Expiratory Volume in One Second (FEV1)
Time frame: Baseline of lead-in study to Week 52 of treatment
Population: The Combined intent to treat (ITT) Population defined as all patients randomized to a treatment group who took at least 1 dose of double-blind investigational product in the lead-in study (LAC-MD-31) and who had a baseline assessment and at least 1 post-baseline assessment of forced expiratory volume in 1 second (FEV1) in LAC-MD-31
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in 1-hour Morning Post-dose Forced Expiratory Volume in One Second (FEV1) | -0.086 Liters | Standard Error 0.017 |
| Aclidinium/Formmoterol 400/12 μg | Change From Baseline in 1-hour Morning Post-dose Forced Expiratory Volume in One Second (FEV1) | 0.198 Liters | Standard Error 0.015 |
| Aclidinium/Formoterol 400/6 μg | Change From Baseline in 1-hour Morning Post-dose Forced Expiratory Volume in One Second (FEV1) | 0.166 Liters | Standard Error 0.015 |
| Aclidinium 400 μg | Change From Baseline in 1-hour Morning Post-dose Forced Expiratory Volume in One Second (FEV1) | 0.112 Liters | Standard Error 0.015 |
| Formoterol 12 μg | Change From Baseline in 1-hour Morning Post-dose Forced Expiratory Volume in One Second (FEV1) | 0.109 Liters | Standard Error 0.015 |
Other Pre-specified
Change From Baseline in Morning Predose (Trough) Forced Expiratory Volume in One Second (FEV1)
Time frame: Baseline of lead-in study to Week 52 of treatment
Population: The Combined intent to treat (ITT) Population defined as all patients randomized to a treatment group who took at least 1 dose of double-blind investigational product in the lead-in study (LAC-MD-31) and who had a baseline assessment and at least 1 post-baseline assessment of forced expiratory volume in 1 second (FEV1) in LAC-MD-31
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Morning Predose (Trough) Forced Expiratory Volume in One Second (FEV1) | -0.101 Liters | Standard Error 0.017 |
| Aclidinium/Formmoterol 400/12 μg | Change From Baseline in Morning Predose (Trough) Forced Expiratory Volume in One Second (FEV1) | 0.038 Liters | Standard Error 0.015 |
| Aclidinium/Formoterol 400/6 μg | Change From Baseline in Morning Predose (Trough) Forced Expiratory Volume in One Second (FEV1) | 0.005 Liters | Standard Error 0.015 |
| Aclidinium 400 μg | Change From Baseline in Morning Predose (Trough) Forced Expiratory Volume in One Second (FEV1) | 0.030 Liters | Standard Error 0.015 |
| Formoterol 12 μg | Change From Baseline in Morning Predose (Trough) Forced Expiratory Volume in One Second (FEV1) | 0.004 Liters | Standard Error 0.015 |
Other Pre-specified
Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score
St George's Respiratory Questionnaire (SGRQ) measures COPD-specific health outcomes and consists of 3 dimension scores (symptom, activity and impact). SGRQ total score is the sum of these scores and ranges from 0 (best health status) to 100 (worst health status).
Time frame: Baseline of lead-in study to Week 52 of treatment
Population: The Combined intent to treat (ITT) Population defined as all patients randomized to a treatment group who took at least 1 dose of double-blind investigational product in the lead-in study (LAC-MD-31) and who had a baseline assessment and at least 1 post-baseline assessment of forced expiratory volume in 1 second (FEV1) in LAC-MD-31
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score | -1.862 Scores on a scale | Standard Error 0.945 |
| Aclidinium/Formmoterol 400/12 μg | Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score | -3.646 Scores on a scale | Standard Error 0.861 |
| Aclidinium/Formoterol 400/6 μg | Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score | -5.527 Scores on a scale | Standard Error 0.819 |
| Aclidinium 400 μg | Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score | -4.306 Scores on a scale | Standard Error 0.847 |
| Formoterol 12 μg | Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score | -4.059 Scores on a scale | Standard Error 0.853 |
Other Pre-specified
Transition Dyspnea Index (TDI) Focal Score at End of Study
The TDI measures the change from baseline in severity of breathlessness in symptomatic patients. The TDI contains a rating for 3 categories (functional impairment, magnitude of task, magnitude of effort). TDI scale ranges from -3 (major deterioration) to +3 (major improvement) including a 0 score to indicate no change. The 3 categories are added to obtain a focal score ranging from -9 (including 0) to +9.
Time frame: Baseline of lead-in study to Week 52 of treatment
Population: The Combined intent to treat (ITT) Population defined as all patients randomized to a treatment group who took at least 1 dose of double-blind investigational product in the lead-in study (LAC-MD-31) and who had a baseline assessment and at least 1 post-baseline assessment of forced expiratory volume in 1 second (FEV1) in LAC-MD-31
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Transition Dyspnea Index (TDI) Focal Score at End of Study | 0.731 Scores on a scale | Standard Error 0.277 |
| Aclidinium/Formmoterol 400/12 μg | Transition Dyspnea Index (TDI) Focal Score at End of Study | 1.812 Scores on a scale | Standard Error 0.251 |
| Aclidinium/Formoterol 400/6 μg | Transition Dyspnea Index (TDI) Focal Score at End of Study | 1.742 Scores on a scale | Standard Error 0.235 |
| Aclidinium 400 μg | Transition Dyspnea Index (TDI) Focal Score at End of Study | 1.596 Scores on a scale | Standard Error 0.241 |
| Formoterol 12 μg | Transition Dyspnea Index (TDI) Focal Score at End of Study | 1.324 Scores on a scale | Standard Error 0.246 |